The proposed research project is aimed at obtaining a fuller understanding of the physiological mechanisms controlling parietal cell function. An isolated parietal cell system was chosen because it allowed the parietal cell to be removed from the influences of its mucosal environment and separated from other cellular elements. Methods have been developed for the dispersion of fundic mucosal cells; for separation of an enriched parietal cell fraction; for monitoring the physiological response of the parietal cell using oxygen uptake, aminopyrine accumulation, and morphological transformation; and for determining the cyclic AMP response to stimulation. Methods are being developed for studying the direct interaction of radiolabeled hormones with their specific cell receptors. With these methods the following problems are under study: 1) the direct actions of histamine, gastrin, and cholinergic agents on parietal cells and the interactions that occur between these agents, 2) the effects of anticholinergics and H2-receptor antagonists on secretagogue actions and interaction, 3) the effects of gastrointestinal hormones and other agents on basal and stimulated parietal cell function, 4) the comparison of biological potency of gastrin analogues, 5) evaluation of the role of cyclic nucleotides in mediating hormone action, and 6) study of the mechanism of inhibition of parietal cell function by the prostaglandins.